AIDS-related Kaposi sarcoma (KS) is the most common HIV-associated cancer in sub-Saharan Africa. Even in the modern antiretroviral therapy (ART) era, survival after a diagnosis with KS in sub-Saharan Africa is poor, with a three year survival rate in some countries of only 30%. Timely treatment has been hampered in low- and middle- income countries (LMICs) due to lack of resources that are needed for prompt and accurate KS diagnosis. In this project, we propose a new diagnostic approach that uses a smartphone confocal microscope to provide timely diagnosis of KS. The portable nature of the device means that it can be brought into the field, rather than requiring patients in rural areas t travel long distances for KS diagnosis. In our approach, KS- suspected skin lesions are imaged in vivo with a smartphone confocal microscope in a short procedural time (expected imaging time < 10 minutes). Confocal images can be immediately sent to an expert confocal image reader over the cellular network for image reading, or an automated image analysis application implemented in the smartphone can be used to render a diagnosis. As a result, the diagnosis is delivered to the patient in a timely manner and the treatment is initiated while the patient is stil at the local clinic. In Aim 1, we will develop a smartphone confocal microscope. We will use a reflectance confocal microscopy technique, slit spectrally encoded confocal microscopy (Slit-SECM), which can acquire two-dimensional images by using inexpensive light source and the imaging sensor in the smartphone. We will optimally design the smartphone confocal microscope, fabricate it, and test it for imaging performance. In Aim 2, we will evaluate clinical utility of the smartphone confocal microscope to diagnose KS in Uganda. Skin lesions suspected to be KS will be imaged with the smartphone confocal microscope, and confocal images will be compared with corresponding histologic images, which is the current gold standard. In a case control study, diagnostic sensitivity and specificity will be tested. While thi project focuses on diagnosing KS in LMICs, in future this same approach can be adapted for diagnosis of other diseases in both resource poor and resource rich settings. For example, during melanoma diagnosis and treatment, the smartphone confocal microscope could be adapted to image melanoma lesions non-invasively to guide biopsy and surgical treatment. In conjunction with an endoscopic imaging optics, the smartphone confocal microscope can be used for screening of early-stage cervical cancers. We strongly believe that the smartphone confocal microscopy will greatly improve the early diagnosis of a range of conditions, with the ultimate goal of helping to reduce health disparity around the globe.